It has been previously shown that short-term and long-term exposures to gaseous pollutants alter mucociliary transport in the airways. However, the underlying mechanisms have been elucidated. The overall objective of this proposal is to determine the functional causes of abnormal mucociliary transport resulting from short-term and long-term exposures to concentrations of SO2 and O3 approximating ambient levels. The respective roles of ciliary function, and the quantity (rate of secretion) and in the development of the pollutant-induced impairment of mucociliary transport will be investigated by in vivo an in vitro techniques using the sheep as the experimental model. These methods include the determination of 1) tracheal mucociliary transport rates by observing radiographically the motion of radiopaque teflon particles, 2) the quantity of tracheal secretions by estimating the protein and acid glycoprotein concentrations in respiratory fluid washed out from an isolated tracheal segment, 3) the rheologic properties of airway secretions by using a micro-double capillary technique which permits measurements of small samples directly obtained from the lower airways, 4) ciliary function as assessed by the measurement of ciliary beat frequency of tracheal cells obtained by brushing and observed under the microscope with the aid of a TV-camera, and 5) histologic examination of the airway mucosa. In addition, the possibility that the effects of pollutants on mucociliary function are mediated by changes in the pH of airway secretions, the liberation of chemical mediators and/or a vagal reflex mechanism will be evaluated. We expect the results of these experiments to provide a better understanding of the early stages of SO2 and O3 induced airway damage and thus elucidate the pathogenesis of chronic airway changes. In addition, such new information on the pathogenesis of pollutant-induced mucociliary dysfunction in the airways may be applicable to other forms of airway disease and used to develop new therapeutic approaches.